The human dentition is a typical diphyodont mammalian system with tooth replacement of most
positions. However, after dental replacement and sequential molar development, the dental lamina
undergoes apoptosis and fragments, leaving scattered epithelial units (dental lamina rests; DLRs).
DLRs in adult humans are considered inactive epithelia, thought to possess limited capacity for further
regeneration. However, we show that these tissues contain a small proportion of proliferating cells
(assessed by both Ki67 and PCNA) but also express a number of common dental stem cell markers
(Sox2, Bmi1, β-catenin and PH3) similar to that observed in many vertebrates that actively, and
continuously regenerate their dentition. We compared these human tissues with the dental lamina of
sharks that regenerate their dentition throughout life, providing evidence that human tissues have the
capacity for further and undocumented regeneration. We also assessed cases of human ameloblastoma
to characterise further the proliferative signature of dental lamina rests. Ameloblastomas are assumed
to derive from aberrant lamina rests that undergo changes, which are not well understood, to form a
benign tumour. We suggest that dental lamina rests can offer a potential source of important dental
stem cells for future dental regenerative therapy. The combined developmental genetic data from the
shark dental lamina and ameloblastoma may lead to the development of novel methods to utilise these
rested populations of adult lamina stem cells for controlled tooth replacement in humans.